The long-term objective of this proposal is to enhance the treatment and outcome of anorexia nervosa (AN) and to develop a network of research and training centers to support innovative research in AN. Research on the treatment of AN has lagged that of other conditions, even other eating disorders such as bulimia nervosa, hence it is important to test potentially effective treatments in a large scale study so as to provide a baseline for future studies. The focus of this proposal is on adolescent AN. Successful early treatment is likely to reduce the prevalence of chronic AN with its high rates of morbidity and mortality and high health care costs. The most promising treatment for adolescent AN is a specific form of family therapy, (the Maudsley approach) called here, behavioral family therapy (BFT). This treatment is focused on the disordered eating behavior that characterizes AN and enables parents to refeed their child. Additionally, there is preliminary evidence that fluoxetine may be useful in reducing comorbid psychopathology and enhancing maintenance in AN. However, there has been no placebo controlled study of fluoxetine in adolescent AN. Moreover, although there have been several small-scale studies of BFT there has been no controlled comparison with another form of family therapy. Hence, we propose to use systems family therapy (SFT) which has been developed and manualized to represent the type of family therapy practiced in the community. We propose to randomly allocate 240 adolescents aged 12-18 years with AN and their families to one of 4 groups: BFT + placebo;BFT + fluoxetine;SFT + placebo;and SFT + fluoxetine. Medication will be continued for 6-months beyond the end of family therapy to assess medication effects on the maintenance of therapeutic gains. Treatment and assessment will be carried out at 6 clinical sites with 40 subjects per site with separate data and coordinating centers. The treatment sites will follow common assessment and treatment protocols with detailed monitoring of recruitment, treatment, assessment and human subjects procedures by the coordinating center. The results of this study should provide guidance to clinicians concerning optimal treatment approaches for adolescent AN. From the public health perspective, development of effective treatments for adolescents will reduce the morbidity, mortality, and high costs associated with chronic AN.